The University of Minnesota is seeking $18 million in state investment for a new program intended to advance the state’s economy and tackle some of its most pressing challenges. If funded, MnDRIVE (for the Minnesota Discovery, Research and InnoVation Economy) will get rolling in 2014. But U faculty are already leaders in these four targeted areas: food security, neuromodulation, robotics, and bioremediation.
By Greg Breining and Rich Broderick
Photographs by Sara Rubinstein
Treating Brain Conditions
“For many neurological diseases—and there are a lot of them and they affect lots of people and cost a lot of money—we do not have many good tools yet to improve function, let alone cure patients,” says Timothy Ebner
(B.S. ’71, M.D. ’79, Ph.D. ’79), head of the Department of Neuroscience at the University of Minnesota. But that could soon change with advances in neuromodulation, a class of therapeutic techniques in which the activity of brain cells and circuits are modulated in ways that relieve symptoms and even cure illness.
Neuromodulation is already used with success in treating patients with Parkinson’s disease, but the techniques also hold promise for Alzheimer’s, chronic pain, Tourette’s syndrome, stroke, dystonia, and even difficult-to-treat psychiatric problems like schizophrenia and obsessive compulsive disorder.
In recent years the U has been ramping up its neuromodulation efforts, Ebner says, hiring faculty specializing in the field and initiating research into a number of disorders, including a clinical trial under way into the possible use of neuromodulation to treat refractory depression—the kind that does not respond to medication.
Neuromodulation also holds promise for treating episodic ataxia, a disorder in which patients experience temporary but often debilitating loss of motor control and balance. The disorder is caused by dysfunction in the cerebellum, and one of its debilitating aspects is its unpredictability. Armed with the knowledge that episodic ataxia can be triggered by caffeine for patients who have the disorder, Ebner’s research team induced episodes in mice specifically bred to develop the disease, monitoring brain activity in the mice with imaging technology.
They discovered that, during an attack, some neurons oscillate so strongly that they become impervious to normal brain signals. As the oscillations spread through the cerebellum, the mice displayed classic symptoms of ataxia. When the oscillations came to a halt, so did the symptoms. Though neuromodulation techniques cannot yet treat episodic ataxia, such advances make treatment, or perhaps even a cure, a distinct possibility.
Meanwhile, Ebner stresses the economic potential of neuromodulation for Minnesota. The state’s medical devices industry is already a leader in the field, with Medtronic alone accounting for 59 percent of market share for neurostimulation devices, followed by St. Jude Medical and Boston Scientific. Today, these three companies generate revenue of about $2.3 billion from this particular market, but total sales from neuromodulation are expected to rise to nearly $15 billion worldwide within five or six years. With proper investment, Minnesota could find itself at the forefront of that growth.
Says Ebner: “It would be nice if [the state] were still getting about 50 percent of that.”
Big Plans for Mini-Robots
, a Morse-Alumni Distinguished Professor in the College of Science and Engineering, likes to keep a couple of small robots on chairs next to her desk.
Manufactured by French company Aldebaran, the blue and orange NAO (pronounced “now”) robots were specifically developed to play in an annual robot soccer tournament. The reason Gini, associate head of the Department of Computer Science & Engineering whose research areas include artificial intelligence (AI) and robotics, keeps the toylike devices on display is twofold. First, outfitted with cameras and face- and communication-recognition software, the 23-inch-high robots embody a state-of-the-art answer to making robotic devices fully mobile and interactive. Second, the NAO robots are likely to draw the interest of a certain student demographic Gini wants to attract to her field.
“Because they’re cute and look like children, girls are more likely to be interested in them,” she explains.
Gini got into robotics more than 30 years ago by way of a fellowship in Stanford University’s AI laboratories. At the time, the entire field was focused on industrial uses of stationary robotic devices, but her team began to insert cameras into the equipment to help control motion. Mobility soon outstripped manipulation as the cutting edge of robotics; today, Gini says, the forefront of research is in robots that interact with other robots—or with people—based on a constant flow of two-way feedback. “With distributed robotics, you can have many robots assigned specialized tasks and working together, or several robots doing the same task but operated by one person,” Gini explains.
Industrial uses for robotics will continue to grow, but Gini expects major growth in nonindustrial areas as well, such as automated flying robots to check crops or traffic. “The technology for this is ready; it will just take time to commercialize it,” she says. “And on the medical front, there’s continuing development of mini-robots that can be inserted into the body, not just for surgery, but for diagnostic procedures.”
Although the large computer companies in Minnesota are gone, they left behind “a creative workforce that went on to start their own companies in programming, software, design, and medical devices. Robotics are included in all of these fields,” she says. And many have strong U of M connections, including ReconRobotics, whose micro-robot systems are based on technology developed at the U.
Gini also believes robotics offers a special pedagogical advantage. “I am very passionate about education, and I think robotics presents unique potential as a tool to engage the younger generation,” she says. “Students are already hooked in with things like smart phones. I just take them a step further and ask, ‘Do you want to be a user of technology or an inventor of technology?’
“Most of them will answer: ‘An inventor of technology.’ ”
Protecting the Food Supply Chain
A global food system is vulnerable at many points and from many causes, whether drought, wars, embargoes, terrorism, climate change, or foodborne illness. Better protecting that system is one of Francisco Diez-Gonzalez
Meeting that challenge is especially important to Minnesota, where food and agriculture make up the state’s second-largest industry, with 80,000 farms and 2,300 food companies generating more than $15 billion in agricultural products each year. And it requires a holistic approach, tapping researchers working on supply chain analysis, new food processing and preservation solutions, and novel animal health and welfare studies. “We’re thinking of bringing new leaders, new innovators, and we’re going to be looking at the whole aspect of food supply,” says Diez-Gonzalez, a professor of food safety microbiology at the University of Minnesota.
Diez-Gonzalez’s specialty is identifying, tracking, and controlling the organisms, such as E. coli and salmonella, responsible for foodborne illness. Industrial-scale farming and trade spread pathogens around the world. “We are seeing more and more foodborne outbreaks that are actually related to international trade,” he says. For example, the 2011 E. coli contamination of organic bean sprouts in Germany killed 53 people and sickened some 4,000 in several countries.
Yet large industrial farms aren’t solely responsible for foodborne disease. Consumer interest in local and “natural” foods, such as unpasteurized milk, creates other contamination issues. “This is an issue we thought was settled many, many decades ago,” Diez-Gonzalez says. “But because people started believing that raw milk was good for you, we’re seeing increased numbers of people getting sick with this.”
Much of Diez-Gonzalez’s current research involves a family of pathogens known as enterohemorrhagic E. coli. Unknown before 1982, it is now a common and deadly bacterial contaminant of the global food supply. Diez-Gonzalez has been investigating how E. coli interacts with plant tissues at the molecular and genetic level to attach, survive, and proliferate on produce. Recent breakthroughs in technology allow scientists to analyze the expression of large numbers of genes simultaneously to determine how microbes metabolize and behave. By better understanding these mechanisms, Diez-Gonzalez hopes to devise new and better ways to decontaminate food before it reaches the consumer.
He’s using similar analysis of the gene expression of salmonella to understand how that disease-causing bacteria stubbornly survives long periods on dry foods, even when subjected to roasting temperatures. He is also fighting microbes with microbes: combatting foodborne illness with bacteriophages, the viruses that attack bacteria. In recent projects, Diez-Gonzalez’s lab has shown that a “cocktail” of bacteriophages effectively kills E. coli on lettuce leaves and surfaces of stainless steel, tile, and plastic.
Says Diez-Gonzalez: “Right now food is one of the ideal topics to invest in for the future of Minnesota—in particular the efforts of the University to make sure that the food products are going to continue to be safe, secure, and abundant.”
Cleaning Polluted Water with Microbes
wants to enlist an army to clean up industrial pollution that, left untreated, would stymie Minnesota industrial development, especially mining and agriculture. His troops are a variety of invisible microbes.
Agriculture, Minnesota’s second-largest industry, and mining, which employs 4,200 in taconite mining alone, both produce water pollution. “My part of this larger project is trying to advance industry while at the same time conserving our environment,” says Sadowsky, director of the University of Minnesota’s BioTechnology Institute.
That’s where the microbes come in. In a process called bioremediation, microorganisms clean up contamination from mining, agriculture, and natural gas exploration.
For example, fish farming in the abandoned open-pit mines of the Iron Range has contaminated the water. Various species of microbes can restore water quality by removing nitrates. “This concept is not novel,” Sadowsky says. “It’s the way a fish tank works to remove nitrogen toxicity.” Different microbes metabolize and remove different materials. “So you have to understand what the microbes do on an individual level, understand what they do together, and then understand the ecology of that system.”
One pressing issue is the anticipated development of sulfide mining for copper and other metals in northeastern Minnesota. This has the potential to produce acidic drainage, nitrate pollution, and heavy metal contamination. “Fortunately, we have a lot of really good faculty here who understand microorganisms and their relationship to metals,” Sadowsky says. “We’d like to harness these microorganisms for some of these mining projects to help minimize environmental impact.”
Fracking—the practice of injecting water, sand, and various hydrocarbons at high pressure into petroleum formations to stimulate the flow of oil—has vastly boosted production of oil and natural gas in the United States. (It has also led to profitable mining of “frac sand” in southeastern Minnesota.) Left untreated, fracking fluids are a threat to drinking and surface water.
Bioremediation may come to the rescue. U of M researchers are developing technologies that encapsulate bacteria in silica materials to degrade the toxins in the fracking fluids “to save water and to avoid allowing those chemicals to enter the environment,” says Sadowsky. “So that’s nature working for you, because petroleum is a natural product and microbes have evolved to degrade those natural products.”
Investment in the U’s bioremediation research would allow the hiring of more faculty experts, says Sadowsky. “Right now we have some of the power needed to approach these issues. But having more faculty focused in selected groups that approach these as a team is a much more effective way of dealing with this research.”